Modulation of Presynaptic Calcium Transients by Metabotropic Glutamate Receptor Activation: A Differential Role in Acute Depression of Synaptic Transmission and Long-Term Depression

• DOI: 10.1523/jneurosci.22-16-06885.2002
• Publication Date: 2018-04-05T22:40:57Z
• Authors: Guido C. Faas; Hita Adwanikar; Robert W. Gereau; Peter Saggau
• Keywords: Microinjections; Receptor, Metabotropic Glutamate 5; Glycine; Presynaptic Terminals; Excitatory Postsynaptic Potentials; Neural Inhibition; Resorcinols; In Vitro Techniques; Receptors, Metabotropic Glutamate; Hippocampus; Synaptic Transmission; Electric Stimulation; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Animals; Calcium; Calcium Signaling; Fura-2; Microelectrodes; Fluorescent Dyes

Activation of group I metabotropic glutamate receptors (mGluRs) can induce acute depression of excitatory synaptic transmission and long-term depression (LTD) in area CA1 of the rat hippocampus. The underlying mechanisms for both forms of depression are unknown. By measuring presynaptic calcium transients, we show that a reduction in the stimulation-induced presynaptic calcium rise that triggers vesicular release causes the acute depression of transmission by group I mGluRs. In contrast, the mechanism underlying mGluR-induced LTD does not involve a persistent change in stimulation-induced calcium influx. However, analysis of paired-pulse facilitation experiments suggests a presynaptic location for expression of this form of LTD. Furthermore, we show that mGluR-induced LTD can be completely blocked by a specific mGluR5 antagonist, whereas mGluR1 antagonists strongly attenuate the acute depression of transmission. These results support the hypothesis that the acute depression of transmission caused by activation of group I mGluRs involves regulation of stimulation-induced presynaptic calcium transients, whereas mGluR-induced LTD involves a distinct presynaptic modulation downstream of calcium influx.